2. THROMBOSIS - Definition
Thrombosis is the process of formation of solid mass in circulation from the
constituents of flowing blood; the mass itself is called a thrombus.
In contrast, a blood clot is the mass of coagulated blood formed in vitro e.g. in a
test tube Haematoma is the extravascular accumulation of blood clot e.g. into the
tissues.
Haemostatic plugs are the blood clots formed in healthy individuals at the site of
bleeding e.g. in injury to the blood vessel. In other words, haemostatic plug at the cut
end of a blood vessel may be considered the simplest form of thrombosis.
Haemostatic plugs are useful as they stop the escape of blood and plasma, whereas
thrombi developing in the unruptured cardiovascular system may be life-threatening
by causing one of the following harmful effects.
3. Effects
Haemostatic plugs are useful as they stop the escape of blood and plasma, whereas
thrombi developing in the unruptured cardiovascular system may be life-threatening
by causing one of the following harmful effects:
1. Ischaemic injury. Thrombi may decrease or stop the blood supply to part of an
organ or tissue and cause ischaemia which may subsequently result in infarction.
2. Thromboembolism. The thrombus or its part may get dislodged and be carried
along in the bloodstream as embolus to lodge in a distant vessel
4. Pathophysiology
Since the protective haemostatic plug formed as a
result of normal haemostasis is an example of
thrombosis, it is essential to describe
thrombogenesis in relation to the normal
haemostatic mechanism. Human beings possess
inbuilt system by which the blood remains in fluid
state normally and guards against the hazards of
thrombosis and haemorrhage. However, injury to
the blood vessel initiates haemostatic repair
mechanism or thrombogenesis.
Virchow described three primary events which
predispose to thrombus formation (Virchow’s triad):
1. Endothelial injury
2. Altered blood flow
3. Hypercoagulability of blood.
5. 1. ENDOTHELIAL INJURY
The integrity of blood vessel wall is important for maintaining normal blood flow. An
intact endothelium has the following functions:
i. It protects the flowing blood from the thrombogenic influence of subendothelium.
ii. It elaborates a few anti-thrombotic factors (thrombosis inhibitory factors)
iii. It can release a few prothrombotic factors which have procoagulant properties
(thrombosis favouring factors)
6. ROLE OF PLATELETS
Following endothelial cell injury, platelets come to play a central role in normal
haemostasis as well as in thrombosis. The sequence of events is as under
i. Platelet adhesion
ii. Platelet release reaction
iii. Platelet aggregation
7. ROLE OF
COAGULATION
SYSTEM.
Coagulation mechanism is the
conversion of the plasma
fibrinogen into solid mass of
fibrin. The coagulation system is
involved in both haemostatic
process and thrombus
formation.
i. In the intrinsic pathway
ii. In the extrinsic pathway
iii. The common pathway
8. 2. ALTERATION OF BLOOD FLOW
Turbulence means unequal flow while stasis
means slowing.
• Normally, there is axial flow of blood in which
the most rapidly-moving central stream consists
of leucocytes and red cells. The platelets are
present in the slow-moving laminar stream
adjacent to the central stream while the
peripheral stream consists of most slow-moving
cell-free plasma close to endothelial layer
• Turbulence and stasis occur in thrombosis in
which the normal axial flow of blood is
disturbed. When blood slows down, the blood
cells including platelets marginate to the
periphery and form a kind of pavement close to
endothelium (margination and pavementing)
9. 3. HYPERCOAGULABILITY OF BLOOD
The occurrence of thrombosis in some conditions such as in nephrotic syndrome,
advanced cancers, extensive trauma, burns and during puerperium is explained on the
basis of hypercoagulability of blood. The effect of hypercoagulability on thrombosis is
favoured by advancing age, smoking, use of oral contraceptives and obesity.
Hypercoagulability may occur by the following changes in the composition of blood:
i. Increase in coagulation factors e.g. fibrinogen, prothrombin, factor VIIa, VIIIa and
Xa.
ii. Increase in platelet count and their adhesiveness.
iii. Decreased levels of coagulation inhibitors e.g. antithrombin III, fibrin split
products.
10. Origin of Thrombi
Thrombi may arise from the heart, arteries, veins or in microcirculation.
1. CARDIAC THROMBI
Thrombi may form in any of the chambers of the heart and on the valve cusps.
They are more common in the atrial appendages, especially of the right atrium,
and on mitral and aortic valves called vegetations which may be seen in infective
endocarditis and non-bacterial thrombotic endocarditis
2. ARTERIAL AND VENOUS THROMBI
Arterial thrombi:
• Aorta: aneurysms, arteritis.
• Coronary arteries: atherosclerosis.
• Mesenteric artery: atherosclerosis, arteritis.
• Arteries of limbs: atherosclerosis, diabetes
mellitus,
• Buerger’s disease, Raynaud’s disease.
• Renal artery: atherosclerosis, arteritis.
• Cerebral artery: atherosclerosis, vasculitis.
Venous thrombi:
• Veins of lower limbs: deep veins of legs,
varicose veins.
• Popliteal, femoral and iliac veins: postoperative
stage,
• postpartum.
• Pulmonary veins: CHF, pulmonary hypertension.
• Hepatic and portal vein: portal hypertension.
11. Origin of Thrombi
3. CAPILLARY THROMBI. Minute thrombi composed mainly of packed red cells are
formed in the capillaries in acute inflammatory lesions, vasculitis and in disseminated
intravascular coagulation
12. Fate of Thrombus
The possible fate of thrombi can be as under
1. RESOLUTION
Thrombus activates the fibrinolytic system with consequent
release of plasmin which may dissolve the thrombus
completely resulting in resolution.
2. ORGANISATION
If the thrombus is not removed, it starts getting organised.
Phagocytic cells (neutrophils and macrophages) appear and
begin to phagocytose fibrin and cell debris.
3. PROPAGATION.
The thrombus may enlarge in size due to more and more
deposition from the constituents of flowing blood. In this
way, it may ultimately cause obstruction of some important
vessel
4. THROMBOEMBOLISM.
The thrombi in early stage andinfected thrombi are quite
friable and may get detached from the vessel wall.
13. Clinical Effects
These depend upon the site of thrombi, rapidity of formation, and nature of thrombi.
1. Cardiac thrombi. Large thrombi in the heart may cause sudden death by mechanical obstruction of
blood flow or through thromboembolism to vital organs.
2. Arterial thrombi. These cause ischaemic necrosis of the deprived part (infarct) which may lead to
gangrene. Sudden death may occur following thrombosis of coronary artery.
3. Venous thrombi (Phlebothrombosis). These may cause following effects:
i. Thromboembolism
ii. Oedema of area drained
iii. Poor wound healing
iv. Skin ulcer
v. Painful thrombosed veins (thrombophlebitis)
vi. Painful white leg (phlegmasia alba dolens) due to ileofemoral venous thrombosis in
postpartum cases
vii. Thrombophlebitis migrans in cancer.
4. Capillary thrombi. Microthrombi in microcirculation may give rise to disseminated intravascular
coagulation
